The principle goal of this research proposal is to develop the knowledge and skills in cellular immunology, biochemistry and molecular biology necessary for productive independent investigation of the cellular immune response in pregnancy. This goal will be accomplished in two distinct phases. Phase I will be devoted to didactic study in basic immunology and a closely supervised laboratory project designed to develop the knowledge and skills fundamental to independent study of the cellular immune response. The specific aims during Phase I will be: (a) to generate and characterize endothelial cell specific cytolytic T lymphocyte (CTL) lines and clones; (b) to analyze the effector and target cell molecules involved in the CTL-endothelial cell interactions: (c) to generate monoclonal antibodies which inhibit cytolysis by binding to effector/target antigens; (d) to characterize the antigenic molecules biochemically; and if time allows (e) to isolate and clone the genes for interesting cell surface structures. During Phase II the theoretical and technical knowledge gained in Phase I will be applied to independent investigation of cellular immune interactions involved in the success of the fetal-maternal allograft. The molecular mechanisms by which fetal-derived trophoblastic tissue is able to avoid immunologic detection and cytolysis by maternal immunocytes will be investigated using the techniques described in Phase I. Studies will focus on identification, characterization and alteration of specific cell surface molecules involved in lymphocyte-trophoblast interactions.